In the field of clinical analyzers for the testing of liquid analytes, a patient sample is introduced and caused to interact with a reaction chemistry to produce a signal involving the analyte of choice, for detection by a sensing apparatus. A preferred technique used by analyzers involves the so-called dried assay technology whereby patient sample is applied to dried test slide elements, each having a dried reactant layer. Analyzers and test elements using this technology include those manufactured by Eastman Kodak Company, both under the trademark "EKTACHEM.TM.".
In a conventional operation, a patient sample is conveyed to a processing station within an analyzer at which time a patient sample is dispensed onto the test element. The sample is dispensed by means of a point source, usually a disposable pipette tip, which is positioned a short distance above the test element surface and has a tip orifice from where the sample is expelled (or metered) onto the sample. A metering tip method of dispensing patient liquid is described in U.S. Pat. No. 5,143,849. There are a number of problems relating to a metering technique such as those typically described.
First, it is important to understand that sample delivered from a point source has to spread horizontally, as well as vertically, through the predetermined test volume of the test element. The need for both directions of spreading introduces the possibility of flow irregularities.
Second, the reliability of test results is impacted by the sensitivity occurring due to differences in the makeup of samples between patients. For example, a patient may have a serum, plasma or whole blood sample that may contain a high fat content, (i.e.: containing a higher percentage of lipids and lipo-proteins than a "normal" patient). These sorts of differences are not, however, limited to non-average patients; differences in samples between patients in the so-called "normal" range may also impact the accuracy of test results.
In some cases, the presence of varying amounts of biological components and salts in the patient sample can produce a variation in the sample's viscosity, surface tension and contact angle, impacting its ability to outwardly spread in a uniform manner when dispensed as a drop from a suspended pipette tip onto a test element. Nonuniformity in the spreadability of a patient liquid may affect the accuracy of the detection of the analyte of choice, especially if the analyzer detection means is focused on only a portion of the chemistry portion of the test element onto which a patient sample has been dispensed. This type of nonuniformity is possible with any body fluid, such as blood serum, urine, etc., and may extend as well to control or calibration liquids that are commonly utilized in known clinical analyzers.
The above problems are generally known as "matrix effects" and are based on differences in patient liquid samples, as well as sample interaction with the spreading layer of the chemistry portion of a test element. The spreading layer assists in the migration of the liquid sample across the chemistry portion of the element and in general it works well to counter these effects. An example of a spreading layer is described in greater detail in U.S. Pat. No. 3,992,158.
However, the requirement that a spreading layer be added to the chemistry portion of a test element to promote sample migration is expensive and complex. In addition, and notwithstanding the use of a spreading layer, point source dispensing systems have other drawbacks. For example, it is usually required that an additional volume of patient liquid be dispensed onto the test element to provide a sufficiently uniform detection or read area. Typically as much as 10 microliters of a patient liquid can be required to produce an effective read area having a diameter of 3 mm. This, in turn, also requires that the chemistry portion of the test element be provided with a larger surface area to accept the additional volume of patient liquid dispensed onto the test element. Further, the dispensing of additional quantities of patient liquid from a point source above the test element also increases the probability of outwardly diffusing or washout of the reaction chemistry, effectively diluting the chemical portion of the test element.
There are other effects which may produce test variability that result from dispensing a volume of liquid sample from a point source. The ability of a point source, such as a pipette tip, to adequately target onto a test element so that it can be analyzed is directly influenced by flow characteristics of the liquid to be tested. These characteristics are affected by factors such as the viscosity, surface tension, contact angle and temperature of the liquid, the volume dispensed, shape of the tip nozzle, the distance the tip is suspended above the test element, the centering of the tip above the test slide, and the makeup of the sample to be tested. Other factors such as the amount of ambient air flow in the vicinity of the dispensed liquid, must also be considered, and all factors may impact upon the accuracy of results. In addition, it is also known that liquid dispensed by a suspended point source has a tendency to move up the exterior surface of the dispensing container, rather than down onto the test element designed to receive the liquid. This problem, known as perfusion, has been an occasional but persistent problem with clinical analyzers using the dispensing means described, altering the volume of liquid that is subsequently dispensed. In addition, the horizontal or outward flow of a point source dispensed liquid varies over time, affecting in particular rate-type chemistries which are also time dependent.
There is, therefore, a need to provide a metering method which will allow patient liquid to be deposited onto a test element without the variability in testing results which are possible using known point source techniques.
There is also a need to provide a method of dispensing a smaller quantity of a patient liquid onto a test element in a substantially uniform manner which will minimize the flow characteristics of the dispensed liquid, as well as washout, and produce an effective detection area for an analyzer.
There is a further need to provide a method of dispensing a patient sample to a test element which will obviate the current needs of requiring a spreading layer to horizontally and uniformly spread a liquid patient sample over the detection area of a test element, thereby also simplifying their design and manufacture.